21-Methylmelianodiols from Poncirus trifoliata as inhibitors of interleukin-5 bioactivity in pro-B cells

Interleukin (IL)-5 plays an important role in the progression of allergic inflammation. Here, we have isolated 21 alpha-methylmelianodiol and 21 beta-methylmelianodiol from Poncirus trifoliata (L.) Raf., a plant of the Rutaceae family, as the inhibitors of IL-5-dependent growth of Y16 pro-B cells by bioassay-guided fractionation. 21 alpha-Methylmelianodiol and 21 beta-methylmelianodiol inhibited IL-5-dependent growth of Y16 cells in a close-dependent manner with IC50 values of 17 mu M and 15 mu M, respectively. A positive control, tyrphostin AG-490, exhibited an IC50 value of 23 mu M on IL-5 bioactivity. Further, we have documented that 21 alpha-methylmelianodiol and 21 beta-methylmelianodiol cause G1 arrest of IL-5-induced cell cycle progression of Y16 cells, and also reduce IL-5-dependent survival of the cells by apoptosis. This study could provide a pharmacological potential for P. trifoliata in treatment of IL-5-associated inflammatory disorders.